Access

Letters to Nature

Nature 410, 1099-1103 (26 April 2001) | doi:10.1038/35074106; Received 8 December 2000; Accepted 6 March 2001

Open Innovation Challenges

naturejobs

More science jobs
Post a job for free

The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5

Fumitaka Hayashi1, Kelly D. Smith2,3, Adrian Ozinsky2, Thomas R. Hawn2,4, Eugene C. Yi2, David R. Goodlett2, Jimmy K. Eng2, Shizuo Akira5, David M. Underhill2 & Alan Aderem2

  1. Department of Immunology,
  2. Department of Pathology,
  3. Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington 98195, USA
  4. Institute for Systems Biology, 4225 Roosevelt Way NE, Suite 200, Seattle, Washington 98195, USA
  5. Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka. 565-0871, Japan

Correspondence to: Alan Aderem2 Correspondence and requests for materials should be addressed to A.A. (e-mail: Email: aderem@systemsbiology.org).

Top

The innate immune system recognizes pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, but not on the host. Toll-like receptors (TLRs) recognize PAMPs and mediate the production of cytokines necessary for the development of effective immunity1, 2, 3, 4. Flagellin, a principal component of bacterial flagella, is a virulence factor that is recognized by the innate immune system in organisms as diverse as flies, plants and mammals5, 6, 7, 8, 9, 10, 11. Here we report that mammalian TLR5 recognizes bacterial flagellin from both Gram-positive and Gram-negative bacteria, and that activation of the receptor mobilizes the nuclear factor NF-kappaB and stimulates tumour necrosis factor-alpha production. TLR5-stimulating activity was purified from Listeria monocytogenes culture supernatants and identified as flagellin by tandem mass spectrometry. Expression of L. monocytogenes flagellin in non-flagellated Escherichia coli conferred on the bacterium the ability to activate TLR5, whereas deletion of the flagellin genes from Salmonella typhimurium abrogated TLR5-stimulating activity. All known TLRs signal through the adaptor protein MyD88. Mice challenged with bacterial flagellin rapidly produced systemic interleukin-6, whereas MyD88-null mice did not respond to flagellin. Our data suggest that TLR5, a member of the evolutionarily conserved Toll-like receptor family, has evolved to permit mammals specifically to detect flagellated bacterial pathogens.